On mutation and namings

Viruses are unusual; unlike other organisms which always use DNA to pass information between generations, viral genetic material isn’t always DNA. Some viruses use RNA, which human cells mostly use to transmit information from the nucleus to the machinery that makes proteins. These differences in the way in which viruses encode their genes have a profound impact on viral evolution. When human cells make copies of themselves, they use proofreading to ensure that the DNA copies are identical to the original code, this reduces the rate of mutation. However, viruses that use RNA to transmit their genes lack this proof-reading capacity, leading to a much higher mutation rate. Whilst this can be deleterious for an individual offspring virus, for the population as a whole it is extremely effective. This comes down to numbers, higher species only produce limited numbers of offspring, so each one needs to be as good possible. Viruses go for safety in numbers, really big numbers. Each infected cell produces approximately 10,000 new viruses. Therefore, there is a huge stock of different offspring, a small number of which will be fitter than their parents. This high degree of mutation means it can be tricky to apply the Linnaean system to group viruses. We can loosely group viruses on a range of different characteristics or the similarity of their genes, but because they change all the bloody time, they are hard to pin down exactly.

Viruses can be named after the disease they cause: influenza virus is named after influenza and yellow fever virus after yellow fever, this is admittedly confusing, but reflects how the disease was known before the causative agent. Alternatively, viruses are named after the part of the body they infect, in Greek to make it sound more sciencey, hence rhinovirus rather than nose virus (rhino is the Greek word for nose). Finally, viruses have been named the geographical region where they were discovered (Ebola after the Ebola river, Lassa after a village in Nigeria). The geographical naming of viruses stopped due to the stigma attached, which is why SARS-CoV-2 took three months to be named and wasn’t called Wuhan virus. Though a different approach has been used recently of using Greek letters for the SARS-CoV-2 variants of concern.

 Excerpt from Infectious: Pathogens and how we fight them

Signalling failure delays training of antibody in early life

 

This may come as a surprise, but there are other viruses that infect our lungs than COVID! One of them is called Respiratory Syncytial Virus (RSV). This innocuously named virus is THE leading cause of hospitalisation in children during winter months, but somehow doesn’t get the same level of attention as its sexier relatives influenza and SARS. One of my colleagues Prof Peter Openshaw has previously suggested it be called ‘deadly killer virus’ to get it the attention it deserves.

One of the interesting aspects about RSV is that it is possible to get re-infected with the same virus. This is unusual because the assumption is mostly that once the immune system has seen a virus once it is then better trained to deal with it in the future, preventing further infections. However, some viruses such as RSV (and also coronaviruses, like the one that causes COVID) can reinfect. We don’t fully understand why this is the case, but one contributing factor is a protein in the blood called antibody. Antibodies are highly specific molecules made by the immune system that can bind and kill viruses.

Antibody molecules are produced by a white blood cell called the B cell, but in order to produce the best possible antibody, B cells need help from another type of cell called the T cell. The conversation between T and B cells happens in the lymph nodes – which is why you get swollen glands after infection or immunisation. In our recent work, ‘Enhanced IL-2 in early life limits the development of TFH and protective antiviral immunity‘ recently published in the Journal of Experimental Medicine we explored this interaction. Specifically, we asked the question are there differences between the T-B cell crosstalk in early life – the time of greatest susceptibility to RSV.

We found that baby mice infected with RSV produce less antibody than adult mice infected with the same dose. This lack of antibody left the mice susceptible to re-infection with the virus. Side by side with the reduction of antibody, there were fewer of the helpful T cells needed to train the B cells. If we specifically removed those helpful T cells (called T follicular helper cells or Tfh) from adult mice before RSV infection, we saw a very similar effect – re-infection.

We dug deeper as to why these handy Tfh cells are not so active in early life. We identified a role for a molecule that cells use to talk to each other called interleukin two (the sequel to the commercially more successful, but less interesting interleukin one). There is more of this molecule sloshing around in early life and it may play a role in training the early immune system what is good and what is bad.

Overall, out findings may help us to develop better vaccines that work from the moment babies are born and stop them catching viruses such as RSV.